The Need for Large-Scale Randomized Evidence Without Undue Emphasis on Small Trials, Meta-analyses, or Subgroup Analyses

Extract

Randomized trials of adequate size and duration designed to test a priori hypotheses represent the most reliable design strategy to detect the most realistically small to moderate therapeutic effects of drugs. Such trials should achieve high adherence to an adequate dose of the drug and a sufficient number of clinical end points to distinguish reliably between the null hypothesis and the most plausible alternative hypothesis of small to moderate benefit or harm.1 With regard to the development of drugs to treat diabetes mellitus, the US Food and Drug Administration (FDA) has developed guidance for industry that somewhat overemphasizes results from meta-analyses of phase 2 trials that were not large enough to test realistic hypotheses about clinical cardiovascular (CV) events.2 Even in aggregate, such results should be considered more as hypothesis formulating than as hypothesis testing. The main need now is for trials that are large enough to have adequate statistical power.

First Page Preview

Figures

Tables

References

Letters

The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with
the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.

Return to: The Need for Large-Scale Randomized Evidence Without Undue Emphasis on Small Trials, Meta-analyses, or Subgroup Analyses

This feature is provided as a courtesy. By using it you agree that that you are requesting the material solely for personal, non-commercial use, and that it is subject to the AMA's Terms of Use. The information provided in order to email this article will not be shared, sold, traded, exchanged, or rented. Please refer to The JAMA Network's Privacy Policy for additional information.

Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.